The broad objective of this study is to understand the role of chromatin structure in the distribution of carcinogen-induced damage to DNA and its subsequent repair in human cells. In summary of the present report, DNA repair synthesis within different structural regions of chromatin was measured by a mathematical analysis of the kinetics of digestion with staphylococcal nuclease and DNase I. In addition gel electrophoresis was used to analyze DNA fragments resistant to these enzymes. It was found that UV-induced DNA repair synthesis in cultured human fibroblasts occurs almost entirely in the linker regions of nucleosomes. Following repair synthesis, 80-85% of the repair-incorporated nucleotides are involved in nucleosome rearrangement yielding a more uniform distribution of repair synthesis in linker and core DNA. A small fraction of the repair-incorporated nucleotides (15-20%) are not involved with this rapid rearrangement and remain nuclease sensitive. Neither the distribution of repair synthesis nor the rate and extent of rearrangement were affected by different UV doses (1.5 - 50 J/m2), the presence of hydroxyurea, or the rate of repair synthesis. Similar results were obtained with two different classes of xeroderma pigmentosum (XP) cells which have been shown to be repair deficient.